Abstract
The association between CCAAT/enhancer binding protein-ε (CEBPE) rs2239633 polymorphism and acute lymphoblastic leukemia (ALL) risk has been reported, but results of previous studies remain controversial and ambiguous. To assess the association between CEBPE rs2239633 polymorphism and childhood ALL risk, a meta-analysis was performed. Based on comprehensive searches of the PubMed, Embase, Chinese National Knowledge Infrastructure (CNKI), and Chinese Biomedical Literature Database (CBM), we identified outcome data from all articles estimating the association between CEBPE rs2239633 polymorphism and childhood ALL risk. The pooled odds ratio (OR) with 95 % confidence intervals (CIs) were calculated. A significant association between CEBPE rs2239633 polymorphism with childhood ALL was found (OR = 1.19, 95 % CI 1.11–1.28, P < 0.01). Subgroup analysis stratified by ethnicity also suggested a significant association between this polymorphism and childhood ALL in the Caucasian subgroup (OR = 1.19, 95 % CI 1.09–1.30, P < 0.01) and Hispanic subgroup (OR = 1.39, 95 % CI 1.18–1.63, P < 0.01). No significant association was observed in the Asian subgroup (OR = 1.05, 95 % CI 0.90–1.22, P = 0.53). The CEBPE rs2239633 polymorphism increased B cell ALL risk (OR = 1.29, 95 % CI 1.15–1.44, P < 0.01) and B hyperdiploid ALL risk (OR = 1.84, 95 % CI 1.40–2.43, P < 0.01). This meta-analysis demonstrated that the CEBPE rs2239633 polymorphism was significantly associated with childhood ALL risk.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Stiller CA, Parkin DM (1996) Geographic and ethnic variations in the incidence of childhood cancer. Br Med Bull 52:682–703
Gombart AF, Shiohara M, Kwok SH, Agematsu K, Komiyama A, Koeffler HP (2001) Neutrophil-specific granule deficiency: homozygous recessive inheritance of a frameshift mutation in the gene encoding transcription factor CCAAT/enhancer binding protein–epsilon. Blood 97:2561–2567
Papaemmanuil E, Hosking FJ, Vijayakrishnan J, Price A, Olver B, Sheridan E et al (2009) Loci on 7p12.2, 10q21.2 and 14q11.2 are associated with risk of childhood acute lymphoblastic leukemia. Nat Genet 41:1006–1010
Prasad RB, Hosking FJ, Vijayakrishnan J, Papaemmanuil E, Koehler R, Greaves M et al (2010) Verification of the susceptibility loci on 7p12.2, 10q21.2, and 14q11.2 in precursor B-cell acute lymphoblastic leukemia of childhood. Blood 115:1765–1767
Vijayakrishnan J, Sherborne AL, Sawangpanich R, Hongeng S, Houlston RS, Pakakasama S (2010) Variation at 7p12.2 and 10q21.2 influences childhood acute lymphoblastic leukemia risk in the Thai population and may contribute to racial differences in leukemia incidence. Leuk Lymphoma 51:1870–1874
Pastorczak A, Górniak P, Sherborne A, Hosking F, Trelińska J, Lejman M et al (2011) Role of 657del5 NBN mutation and 7p12.2 (IKZF1), 9p21 (CDKN2A), 10q21.2 (ARID5B) and 14q11.2 (CEBPE) variation and risk of childhood ALL in the Polish population. Leuk Res 35:1534–1536
Lautner-Csorba O, Gézsi A, Semsei AF, Antal P, Erdélyi DJ, Schermann G et al (2012) Candidate gene association study in pediatric acute lymphoblastic leukemia evaluated by Bayesian network based Bayesian multilevel analysis of relevance. BMC Med Genomics 5:42
Orsi L, Rudant J, Bonaventure A, Goujon-Bellec S, Corda E, Evans TJ et al (2012) Genetic polymorphisms and childhood acute lymphoblastic leukemia: GWAS of the ESCALE study (SFCE). Leukemia 26:2561–2564
Chokkalingam AP, Hsu LI, Metayer C, Hansen HM, Month SR, Barcellos LF et al (2013) Genetic variants in ARID5B and CEBPE are childhood ALL susceptibility loci in Hispanics. Cancer Causes Control 24:1789–1795
Ross JA, Linabery AM, Blommer CN, Langer EK, Spector LG, Hilden JM et al (2013) Genetic variants modify susceptibility to leukemia in infants: a Children's Oncology Group report. Pediatr Blood Cancer 60:31–34
Walsh KM, Chokkalingam AP, Hsu LI, Metayer C, de Smith AJ, Jacobs DI et al (2013) Associations between genome-wide Native American ancestry, known risk alleles and B-cell ALL risk in Hispanic children. Leukemia 27:2416–2419
Wang Y, Chen J, Li J, Deng J, Rui Y, Lu Q et al (2013) Association of three polymorphisms in ARID5B, IKZF1 and CEBPE with the risk of childhood acute lymphoblastic leukemia in a Chinese population. Gene 524:203–207
Emerenciano M, Barbosa TC, Lopes BA, Blunck CB, Faro A, Andrade C et al (2014) ARID5B polymorphism confers an increased risk to acquire specific MLL rearrangements in early childhood leukemia. BMC Cancer 14:127
Egger M, Smith GD, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634
Akagi T, Thoennissen NH, George A, Crooks G, Song JH, Okamoto R et al (2010) In vivo deficiency of both C/EBPβ and C/EBPε results in highly defective myeloid differentiation and lack of cytokine response. PLoS One 5:e15419
Ryoo H, Kong M, Kim Y, Lee C (2013) Identification of functional nucleotide and haplotype variants in the promoter of the CEBPE gene. J Hum Genet 58:600–603
Acknowledgments
This work was supported by grants from National Natural Science Foundation of China (81300418). This work was also supported by grants from China Postdoctoral Science Foundation funded project (2012M511591, 2013T60708) and The Youth Innovation Fund of the First Affiliated Hospital of Zhengzhou University.
Conflict of interest
None
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Wang, C., Chen, J., Sun, H. et al. CEBPE polymorphism confers an increased risk of childhood acute lymphoblastic leukemia: a meta-analysis of 11 case-control studies with 5,639 cases and 10,036 controls. Ann Hematol 94, 181–185 (2015). https://doi.org/10.1007/s00277-014-2186-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00277-014-2186-x